Table 1 Challenges in diagnosing TB exposure, infection and disease in children
From: Tuberculosis exposure, infection and disease in children: a systematic diagnostic approach
Disease state | Main challenges | Current status & limitations | Recent advances & future prospects |
|---|---|---|---|
Infection | Differentiating between TB exposure (without infection), and TB infection | Current immune-based tests (TST and IGRAs) may not convert to positive until 2–10 weeks after acquiring M. tb infection | Mycobacteria-specific cytokine biomarkers -- alone or in combination (i.e., biosignatures) -- may distinguish between TB exposure (without infection), and TB infection [90] |
Differentiating between infection and subclinical disease | Chest radiography is the first-line imaging modality, but may not reveal abnormalities consistent with TB disease in all cases -- especially those in early states of the continuum of TB | Chest CT, MRI, and PET [91] scan may reveal findings consistent with TB disease before symptoms develop | |
Disease | Detection of TB disease and of drug resistance | Currently available immune-based tests (TST and IGRAs) do not differentiate between infection and disease | Mycobacteria-specific cytokine biomarkers -- alone or in combination -- may distinguish between TB infection and TB disease [90] |
Currently available tests (e.g. NAATs; culture) for bacteriological confirmation have limited sensitivity for detecting M. tb in young children with paucibacillary disease--especially in early states of the continuum of TB | - Xpert MTB/RIF Ultra (Cepheid): next generation, ultrasensitive NAAT for detection of both M. tb & rifamycin resistance; in vitro study demonstrated sensitivity comparable to culture [92, 93]. - GeneXpert Omni (Cepheid): single-cartridge battery-operated platform that is portable/mobile; study pending [93] - Xpert XDR NAAT (Cepheid): study anticipated in 2018 [93] | ||
Specimen collection for bacteriological confirmation currently consists of serial sampling of three gastric aspirates/lavages or induced sputa and requires trained personnel and facilities with airborne infection control | Strategies consisting of “intensive” collection of combinations of various specimens (e.g., nasopharyngeal aspirates; string tests; stool; fine needle aspirate of diseased lymph node) that have similar or superior bacteriological yield, require less training, and may be carried out as an outpatient over 1–2 days | ||
Monitoring response to treatment | Mycobacterial culture is only useful in those children who had positive cultures at time of diagnosis (minority of cases). | Cytokine biomarkers and biosignatures (possibly including IFN-γ, TNF-α, IL-2, IL-6, IL-10 and/or IL-12) [94, 95] | |
18 F-FDG PET/CT is sensitive for the detection of TB disease (in different states of the continuum) and for monitoring response to treatment [91] |